FM-VP4
Identification
- Generic Name
- FM-VP4
- DrugBank Accession Number
- DB05449
- Background
FM-VP4, is a novel hydrophilic phytostanol analogue representing a new class in cholesterol-lowering drugs called cholesterol absorption inhibitors. FM-VP4 has been shown to inhibit cholesterol absorption and to lower plasma LDL-cholesterol and total cholesterol in a broad range of animal species. Additional experiments suggest that FM-VP4 can reduce plasma LDL cholesterol levels and triglyceride levels, reduce weight gain and exert a anti-atherosclerosis effect.
- Type
- Small Molecule
- Groups
- Investigational
- Synonyms
- Disodium ascorbyl phytostanol phosphates
Pharmacology
- Indication
Investigated for use/treatment in hyperlipidemia and cancer/tumors (unspecified).
Monotherapy is recommended for people with marginally high LDL-cholesterol or who cannot be prescribed statins due to drug interactions and safety concerns. Combination Therapy is recommended if statin therapy alone is either insufficient to achieve the guidelines set by the NCEP or there is concern over side effects as Statin doses can be lowered in combination treatment without losing efficacy.
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- Pharmacodynamics
FM VP4 is thought to bind competitively with cholesterol to MDR1 resulting in a synergistic decrease in cholesterol accumlation. Others have suggested that FM VP4 may act by inhibiting a transporter that mediates intestinal absorption of cholesterol.
- Mechanism of action
FM VP4 is thought to bind competitively with cholesterol to MDR1 resulting in a synergistic decrease in cholesterol accumlation. Others have suggested that FM VP4 may act by inhibiting a transporter that mediates intestinal absorption of cholesterol. One study indicates that FM-VP4 inhibits cholesterol accumulation within IEC-6 cells and is most effective at equimolar concentrations with cholesterol, further suggesting that the action of FM-VP4 is likely at the cell surface and not elicited intracellularly.
Target Actions Organism UP-glycoprotein 1 Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Clinical trials have indicated that the drug is well-tolerated.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Not Available
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 1PHN4US15Q
- CAS number
- Not Available
- InChI Key
- Not Available
- InChI
- Not Available
- IUPAC Name
- Not Available
- SMILES
- Not Available
References
- General References
- Thornton SJ, Warburton C, Wasan KM, Kozlowski P: Treatment with a cholesterol absorption inhibitor (FM-VP4) reduces body mass and adipose accumulation in developing and pre-obese mice. Drug Dev Ind Pharm. 2007 Oct;33(10):1058-69. [Article]
- Burnett JR, Huff MW: Cholesterol absorption inhibitors as a therapeutic option for hypercholesterolaemia. Expert Opin Investig Drugs. 2006 Nov;15(11):1337-51. [Article]
- Looije NA, Risovic V, Stewart DJ, Debeyer D, Kutney J, Wasan KM: Disodium Ascorbyl Phytostanyl Phosphates (FM-VP4) reduces plasma cholesterol concentration, body weight and abdominal fat gain within a dietary-induced obese mouse model. J Pharm Pharm Sci. 2005 Aug 24;8(3):400-8. [Article]
- Jia X, Ebine N, Wang Y, Awad AB, Jones PJ: Effects of different phytosterol analogs on colonic mucosal cell proliferation in hamsters. J Nutr Biochem. 2006 Jun;17(6):396-401. Epub 2005 Sep 26. [Article]
- Ebine N, Jia X, Demonty I, Wang Y, Jones PJ: Effects of a water-soluble phytostanol ester on plasma cholesterol levels and red blood cell fragility in hamsters. Lipids. 2005 Feb;40(2):175-80. [Article]
- Ng AW, Lukic T, Pritchard PH, Wasan KM: Development and characterization of liposomal disodium ascorbyl phytostanyl phosphates (FM-VP4). Drug Dev Ind Pharm. 2004 Aug;30(7):739-58. [Article]
- Wasan KM, Choo E, Sivak O, Wallis S, Letchford K, Burt HM, Stewart DJ, Lukic T: Determining the critical micelle concentration of a novel lipid-lowering agent, disodium ascorbyl phytostanyl phosphate (FM-VP4), using a fluorescence depolarization procedure. Drug Dev Ind Pharm. 2004 Aug;30(7):725-30. [Article]
- Burnett JR: FM-VP4 Forbes Medi-Tech. Curr Opin Investig Drugs. 2003 Sep;4(9):1120-5. [Article]
- Ng AW, Lukic T, Pritchard PH, Wasan KM: Development of novel water-soluble phytostanol analogs: disodium ascorbyl phytostanyl phosphates (FM-VP4): preclinical pharmacology, pharmacokinetics and toxicology. Cardiovasc Drug Rev. 2003 Fall;21(3):151-68. [Article]
- Wasan KM, Yau E, Boulanger KD, Ramswamy M, Pritchard PH: Effects of disodium ascorbyl phytostanol phosphates (FM-VP4) on cholesterol accumulation within rat intestinal cells. AAPS PharmSci. 2003;5(1):E6. [Article]
- Lukic T, Wasan KM, Zamfir D, Moghadasian MH, Pritchard PH: Disodium ascorbyl phytostanyl phosphate reduces plasma cholesterol concentrations and atherosclerotic lesion formation in apolipoprotein E-deficient mice. Metabolism. 2003 Apr;52(4):425-31. [Article]
- Wasan KM, Zamfir C, Pritchard PH, Pederson RA: Influence of phytostanol phosphoryl ascorbate (FM-VP4) on insulin resistance, hyperglycemia, plasma lipid levels, and gastrointestinal absorption of exogenous cholesterol in Zucker (fa/fa) fatty and lean rats. J Pharm Sci. 2003 Feb;92(2):281-8. [Article]
- Ramaswamy M, Yau E, Wasan KM, Boulanger KD, Li M, Pritchard PH: Influence of phytostanol phosphoryl ascorbate, FM-VP4, on pancreatic lipase activity and cholesterol accumulation within Caco-2 cells. J Pharm Pharm Sci. 2002 Jan-Apr;5(1):29-38. [Article]
- Wasan KM, Najafi S, Peteherych KD, Pritchard PH: Effects of a novel hydrophilic phytostanol analog on plasma lipid concentrations in gerbils. J Pharm Sci. 2001 Nov;90(11):1795-9. [Article]
- Wasan KM, Najafi S, Wong J, Kwong M, Pritchard PH: Assessing plasma lipid levels, body weight, and hepatic and renal toxicity following chronic oral administration of a water soluble phytostanol compound, FM-VP4, to gerbils. J Pharm Pharm Sci. 2001 Sep-Dec;4(3):228-34. [Article]
- Wasan KM, Peteherych KD, Najafi S, Zamfir C, Pritchard PH: Assessing the plasma pharmacokinetics, tissue distribution, excretion and effects on cholesterol pharmacokinetics of a novel hydrophilic compound, FM-VP4, following administration to rats. J Pharm Pharm Sci. 2001 Sep-Dec;4(3):207-16. [Article]
- External Links
- PubChem Substance
- 347910145
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment High Cholesterol 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
- Not Available
- Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
Drug created at November 18, 2007 18:25 / Updated at June 12, 2020 16:52